Our efforts in the past 22 years to study the chemistry and biology of nucleic acids in an integrated and comprehensive manner will be continued. This program has 2 sections: (1) The physico-chemical properties and interactions of nucleic acids will be studied by NMR or 1H, 13C, 31P, and 19F nuclei with the best spectrometer available. This project is made possible by the organic/biochemical synthesis of short helices, analogs, 13C or 19F labeled nucleic acid, etc., and by computer technology, with graphic facilities for improvement of NMR theory; and (2) The structure and function of nucleic acids having specific, exposed/accessible sequences will be probed by appropriate nonionic oligonucleotide analogs (alkyl phosphotriesters or phosphonates, up to a decamer long) inside the living cells. These compounds form specific duplexes with complementary sequences, penetrate living cells, and resist enzyme degratation. Sequences in tRNA, mRNA, rRNA, and oncogenic viral RNA inside the living cells can be interacted with these analog probes, so that their functions can be analyzed, modified, and controlled. In the past 12 months, six abstracts have been submitted, as well as one paper, entitled, "Computer Programs for Nucleic Acids Studies," describing the computer program on nucleic acids, in Computer Programs in Biomedicine.